Simple Measurement of IgA Predicts Immunity and Mortality in Ataxia-Telangiectasia

Basit Öğe Kaydı
dc.contributor.authorZielen, Stefan
dc.contributor.authorDuecker, Ruth Pia
dc.contributor.authorWoelke, Sandra
dc.contributor.authorDonath, Helena
dc.contributor.authorBakhtiar, Sharhzad
dc.contributor.authorBuecker, Aileen
dc.contributor.authorKreyenberg, Hermann
dc.date.accessioned2024-02-23T13:56:15Z
dc.date.available2024-02-23T13:56:15Z
dc.date.issued2021
dc.departmentNEÜen_US
dc.description.abstractPatients with ataxia-telangiectasia (A-T) suffer from progressive cerebellar ataxia, immunodeficiency, respiratory failure, and cancer susceptibility. From a clinical point of view, A-T patients with IgA deficiency show more symptoms and may have a poorer prognosis. In this study, we analyzed mortality and immunity data of 659 A-T patients with regard to IgA deficiency collected from the European Society for Immunodeficiencies (ESID) registry and from 66 patients with classical A-T who attended at the Frankfurt Goethe-University between 2012 and 2018. We studied peripheral B- and T-cell subsets and T-cell repertoire of the Frankfurt cohort and survival rates of all A-T patients in the ESID registry. Patients with A-T have significant alterations in their lymphocyte phenotypes. All subsets (CD3, CD4, CD8, CD19, CD4/CD45RA, and CD8/CD45RA) were significantly diminished compared to standard values. Patients with IgA deficiency (n = 35) had significantly lower lymphocyte counts compared to A-T patients without IgA deficiency (n = 31) due to a further decrease of naive CD4 T-cells, central memory CD4 cells, and regulatory T-cells. Although both patient groups showed affected TCR-ss repertoires compared to controls, no differences could be detected between patients with and without IgA deficiency. Overall survival of patients with IgA deficiency was significantly diminished. For the first time, our data show that patients with IgA deficiency have significantly lower lymphocyte counts and subsets, which are accompanied with reduced survival, compared to A-T patients without IgA deficiency. IgA, a simple surrogate marker, is indicating the poorest prognosis for classical A-T patients. Both non-interventional clinical trials were registered at clinicaltrials.gov 2012 (Susceptibility to infections in ataxia-telangiectasia; NCT02345135) and 2017 (Susceptibility to Infections, tumor risk and liver disease in patients with ataxia-telangiectasia; NCT03357978)en_US
dc.description.sponsorshipProjekt DEAL; German Federal Ministry of Education and Research (BMBF) [01GM0896, 01GM1111B, 01GM1517C, 01EO1303, 01ZZ1801B]; EU [HEALTHF2-2008-201549]; Novartis; GlaxoSmithKline; LFB; UCB UK; Plasma Protein Therapeutics Association (PPTA),; Care-for-Rare Foundation; PROimmune e.V; Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) [39087428]; UK National Institute of Health Research; Great Ormond Street Hospital Biomedical Research Centreen_US
dc.description.sponsorshipOpen Access funding enabled and organized by Projekt DEAL. The ESID Registry was supported by the German Federal Ministry of Education and Research (BMBF 01GM0896, 01GM1111B, 01GM1517C, 01EO1303 and 01ZZ1801B) EU grant no. HEALTHF2-2008-201549 (EURO-PADnet), the pharmaceutical companies Novartis, GlaxoSmithKline, LFB, and UCB UK, the Plasma Protein Therapeutics Association (PPTA), the Care-for-Rare Foundation, PROimmune e.V, LFB, and the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence StrategyEXC 2155 RESIST-Project ID 39087428. EGD is supported by the UK National Institute of Health Research and the Great Ormond Street Hospital Biomedical Research Centre.en_US
dc.identifier.doi10.1007/s10875-021-01090-8
dc.identifier.endpage1892en_US
dc.identifier.issn0271-9142
dc.identifier.issn1573-2592
dc.identifier.issue8en_US
dc.identifier.pmid34477998en_US
dc.identifier.scopus2-s2.0-85114133044en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage1878en_US
dc.identifier.urihttps://doi.org/10.1007/s10875-021-01090-8
dc.identifier.urihttps://hdl.handle.net/20.500.12452/11145
dc.identifier.volume41en_US
dc.identifier.wosWOS:000692451400001en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherSpringer/Plenum Publishersen_US
dc.relation.ispartofJournal Of Clinical Immunologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectAtaxia-Telangiectasiaen_US
dc.subjectIga Deficiencyen_US
dc.subjectImmunoglobulinsen_US
dc.subjectImmunodeficiencyen_US
dc.subjectLymphopeniaen_US
dc.subjectMortalityen_US
dc.titleSimple Measurement of IgA Predicts Immunity and Mortality in Ataxia-Telangiectasiaen_US
dc.typeArticleen_US

Dosyalar

Koleksiyon

WoS İndeksli Yayınlar Koleksiyonu
PubMed İndeksli Yayın Koleksiyonu
Scopus İndeksli Yayınlar Koleksiyonu